ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

Objective To evaluate the effect of optical body surface monitoring system(OSMS)in setup of intensity modulated radiotherapy(IMRT)for thoracic tumorsand to analyze its relationship with BMI.Methods Thesetup errors of CBCT and location CT with body membrane and the registration errors of OSMS and first body surface reference image without body membrane were obtained in 49 patients with thoracic tumor who received routine intensity modulated radiotherapy.The paired t-test was used to analyze the difference of registration errors between the two image guidance methods.Pearson′s correlation analysis was used to analyze the correlation between CBCT errors and OSMS errors,and Bland-Altman analysis was employed to evaluatethe agreement of the two errors.The correlation and consistency of the two registration errors in patients with different BMI index were analyzed.PTV external marginsby the two registration methods were calculated using Van Herk formula.Results The OSMS and CBCT groups demonstrated significant differences in setup errors in the ventrodorsal direction(P<0.05),while no significant differences were found in the left-right,head-foot translation directions,or RTN rota-tion directions(P>0.05).Although the two methods showed a significant correlation in setup errors(P<0.05),this correlation was only moderate in the head-foot and left-right directions(r=0.500,0.408),weak in the RTN rotation direction(r=0.339),and very weak in the ventrodorsal direction(r=0.152).The limits of agreement(LOA,95％CI)between the two methods were[-0.45,0.45]cm in the left-right direction,[-0.59,0.57]cm in the head-foot direction,and[-0.48,0.40]cm in the ventrodorsal direction,with(-2.08°～2.19°)in the RTN rotation direction.Different BMI levels influenced the results of the two registration methods,particularly in patients with a BMI of 18.5～23.9 kg/m2.In this group,OSMS and CBCT exhibited a strong correlation in the head-foot direction(r=0.731),a moderate correlation in the left-right direction(r=0.512),and weak correlations in the ventrodorsal and RTN rotation directions(r=0.345,0.267).The absolute difference in setup errors between the two imaging systems was 0.4～0.5 cm/2°.Using CBCT and OSMS image guidance,the margins in the left-right,head-foot,and ventrodorsal directions were[0.5 cm,0.7 cm,0.3 cm]for CBCT,and[0.5 cm,0.7 cm,0.5 cm]for OSMS.Conclusion In chest tumor patients with a BMI of 18.5～23.9 kg/m2,OSMS and CBCT image guidance methods show good correlation in the head-foot and left-right directions,but their limits of agreement exceed the clinically acceptable range.OSMS cannot yet replace CBCT for image guidance in chest tumor intensity-modulated radiotherapy.Further improvements to tumor motion surrogates are necessary to enhance the accuracy of OSMS image guidance.

Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective To investigate the efficacy of ganciclovir combined with spleen aminopeptide in treating infectious mononucleosis(IM)and its impact on the immune function of diseased children.Methods Totally 120 diseased children with IM accepted by our hospital from February 2022 to August 2024 were stochastically assigned into a treatment group and a monotherapy group.The monotherapy group received treatment with ganciclovir,while the treatment group received treatment with spleen aminopeptide in addition to the monotherapy group.The efficacy,symptom improvement time,serum inflammatory factors,immune indicators,and biochemical indicators before and after treatment were compared between the two groups.Results The efficacy of the treatment group was better than that of the monotherapy group,and the symptom relief time was shorter than that of the monotherapy group(P＜0.05).After treatment,the serum amyloid A,TNF-α,IL-6,procalcitonin,CD3+T,CD8+T,lactate dehydrogenase,alanine aminotransferase,EBV-DNA,creatine kinase,and white blood cell count in both groups decreased,while CD4+T and CD4+T/CD8+T increased.The amplitude of the treatment group was greater than that of the monotherapy group(P＜0.05).Conclusion The combination of ganciclovir and spleen aminopeptide in treating IM is beneficial for enhancing the immune function of T lymphocytes of diseased children,alleviating inflammatory reactions,improving biochemical indicators,and enhancing efficacy.

Objective To investigate the characteristics of peripheral blood in the treatment of aplastic anemia(AA)with Bushen Shengxue Method and Yiqi Yangxue Method combined with Western medicine.Methods Totally 492 AA patients who were treated in 19 centers including Xiyuan Hospital China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected,and were randomized into three groups:161 cases in the Bushen Shengxue group,164 cases in the Yiqi Yangxue group,and 167 cases in the control group.All three groups were orally administered cyclosporine and androgens.Bushen Shengxue group was given Bushen Shengxue Granules,Yiqi Yangxue group was given Yiqi Yangxue Granules,and the control group was given placebo(half dosage of Bushen Shengxue granules).The general data,overall efficacy,and peripheral blood at the 1st month,the 4th month,and 6th month after treatment were analyzed.Results The total effective rate of Bushen Shengxue group was 98.8％(159/161),which was significantly higher than that of Yiqi Yangxue group(79.9％)and the control group(61.7％),with statistical significance(P＜0.001);The total effective rate of Yiqi Yangxue group was significantly higher than that of the control group(P＜0.001).Compared with before treatment,the hemoglobin(HGB)levels of all three groups of patients significantly increased after treatment(P＜0.001,P＜0.01),and the platelet levels of Bushen Shengxue group and the control group significantly increased after treatment(P＜0.001);after treatment,the HGB levels in the three groups were ranked from high to low as the Bushen Shengxue group,Yiqi Yangxue group and the control group(P＜0.01).25％of patients had HGB levels exceeding 20％of baseline values,Bushen Shengxue group took 1 month,while Yiqi Yangxue group and control group took 4 months;25％of patients had an increase in HGB levels exceeding 50％of the baseline value,Bushen Shengxue group took 6 months,while Yiqi Yangxue group and control group took more than 6 months.At 6 months,the number of patients with HGB elevation exceeding 20％and 50％of baseline values in Bushen Shengxue group was higher than that in Yiqi Yangxue group and the control group(P＜0.05,P＜0.001).25％of patients had white blood cell elevation exceeding 50％of the baseline value,Bushen Shengxue group took 4 months,Yiqi Yangxue group took 6 months,and the control group took more than 6 months.25％of patients showed an increase in platelet levels exceeding 100％of the baseline value,Bushen Shengxue group took 4 months,while Yiqi Yangxue group and control group took 6 months;at 6 months,the number of patients in Bushen Shengxue group and Yiqi Yangxue group with platelet elevation exceeding 20％of the baseline value was significantly higher than that in the control group(P＜0.01,P＜0.05).Conclusion Bushen Shengxue method combined with Western medicine intreating AA is better than the method of Yiqi Yangxue method combined with Western medicine.In terms of improving HGB,it is reflected in shortening the recovery time and increasing the number of beneficiaries,and the dosage can affect the recovery time and the number of beneficiaries at the same time;in terms of improving white blood cell and platelet,it is reflected in shortening the recovery time,and the dosage can affect the recovery time.

Objective:To explore the clinical feature and genetic variation of NPHS1 variant-associated nephropathy ( NPHS1-VAN) in Chinese patients. Methods:This study was a case-series analysis. Patients with NPHS1-VAN, who were treated and/or followed in the Department of Pediatrics, Nanfang Hospital, Southern Medical University between 2018 and 2023 were recruited into this study. Genotype, phenotype and their relationship were analyzed. Results:Nine NPHS1-VAN patients from 8 non-consanguineous Chinese families were collected, including 5 males and 4 females. There were 7 cases with an onset age within 3 months and 2 cases with an onset age of 6 months and 13 years, respectively. Seven patients harbored compound heterozygous variants, two had homozygous variants, including 8 missense variations,3 frameshift variants, and 1 splicing site variant. Four patients in 3 families harbored missense variant c.928G>A, two of them experienced spontaneous remission of proteinuria at the age of 1 year and 2 years, respectively, another one had persistent proteinuria and entered end stage renal disease (ESRD) at 11 years old. The other one had an onset age of 6 months with no response to steroids initially. She got complete remission by tacrolimus administered, but relapse frequently and partially responded to steroids later. Two patients of this group died, one of them died of respiratory failure 3 days after birth. Excessive amniotic fluid and fetal edema were acknowledged at 28 weeks of gestational age. He harbored compound heterozygous variants of NPHS1, c.1135C>G (R379G) and c.1339G>A (E447K). His mother previously experienced fetal death at 28 weeks gestational age for her first pregnant and stillborn at 36 weeks of gestational age for her second pregnant, respectively. One patient in this study who harbored homozygous variant of c.1339G>A (E447K) presented with a mild phenotype, onset age was 13 years old and didn't progress to ESRD yet at 21 years. Thus, variant E447K was hypothesized to be weakly pathogenic, while R379G may be strongly pathogenic with a risk of death. Five novel variants were identified in this group of patients, 3 missense variants (c.1135C>G, c.1157A>T, c.3197T>A) and 2 frameshift variants (c.709_710delCT, c.3193delG). Renal biopsy was performed in 4 cases, of whom two were focal segmental glomerular sclerosis and another two were minimal change disease. Conclusions:NPHS1-VAN possesses remarkable clinical and genetic heterogeneity. Five novel variants were identified. Missense variant is the most common variant type and c.928G>A is the most common one in this group of patients, in consistent with previous report in China. Children harbor c.928G>A may have a mild phenotype with possible spontaneous remission and may be response to steroids and calcineurin inhibitor. Variant c.1135C>G (R379G) may have a strong pathogenicity, and patient who harbors this variant may have a severe phenotype.

Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.

Objective To explore the applicative value of spectral CT in increasing positive rates of lung cancer puncture and reducing complications during CT guided percutaneous transthoracic needle biopsy(PTNB).Methods The pathological results and complica-tion incidences of 260 PTNB patients were analyzed retrospectively.All patients were divided into three groups:group A(conventional CT group,103 cases)used a scheme based on conventional enhanced CT;group B(PET/CT group,84 cases)used a scheme combining the maximum standardized uptake value(SUVmax)with conventional enhanced CT;group C(spectral CT group,73 cases)used a scheme of quantitative spectral CT parameters and images.Results Group A included 103 cases in total,of which 87 were positive(84.47％),41 pneumothorax(39.81％),and 31 hemorrhage(30.10％).Group B totaled 84 cases,including 82 positive cases(97.62％),19 cases of pneumothorax(22.62％),and 11 cases of hemorrhage(13.10％).Group C was of 73 cases,including 70 positive cases(95.89％),16 cases of pneumothorax(21.92％),and 10 cases of hemorrhage(13.70％).There were statistically significant differ-ences in biopsy positive rates,pneumothorax incidences,and hemorrhage incidences among groups A,B,and C(P＜0.05).There were also statistically significant differences in biopsy positive rates,pneumothorax incidences,and hemorrhage incidences between groups A and B or groups A and C(P＜0.016 7),respectively.However,no statistically significant differences were found between groups B and C in biopsy positive rates,pneumothorax incidences,and hemorrhage incidences(P＞0.016 7).Conclusion Spectral CT can improve the positive rate of lung cancer and reduce the risk of pneumothorax and hemorrhage with PTNB.

Objective To investigate the efficacy of ganciclovir combined with spleen aminopeptide in treating infectious mononucleosis(IM)and its impact on the immune function of diseased children.Methods Totally 120 diseased children with IM accepted by our hospital from February 2022 to August 2024 were stochastically assigned into a treatment group and a monotherapy group.The monotherapy group received treatment with ganciclovir,while the treatment group received treatment with spleen aminopeptide in addition to the monotherapy group.The efficacy,symptom improvement time,serum inflammatory factors,immune indicators,and biochemical indicators before and after treatment were compared between the two groups.Results The efficacy of the treatment group was better than that of the monotherapy group,and the symptom relief time was shorter than that of the monotherapy group(P＜0.05).After treatment,the serum amyloid A,TNF-α,IL-6,procalcitonin,CD3+T,CD8+T,lactate dehydrogenase,alanine aminotransferase,EBV-DNA,creatine kinase,and white blood cell count in both groups decreased,while CD4+T and CD4+T/CD8+T increased.The amplitude of the treatment group was greater than that of the monotherapy group(P＜0.05).Conclusion The combination of ganciclovir and spleen aminopeptide in treating IM is beneficial for enhancing the immune function of T lymphocytes of diseased children,alleviating inflammatory reactions,improving biochemical indicators,and enhancing efficacy.

Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.